Through its interaction with receptors borne on neuronal and other cells, 5-hydroxytryptamine (5-HT or serotonin) exerts various physiological effects. Imbalances in this interaction are believed to be responsible for such conditions as anxiety, hallucination, migraine, chemotherapy-induced nausea and for disorders in sexual activity, car diovascular activity and thermoregulation, among others. From an improved understanding of the 5-HT receptor population, it is apparent that these effects are mediated selectively through individual types and subtypes of the 5-HT receptors. Migraine, for example, has been treated with ergolamine, dihydroergotamine, methylsergide and, most recently, sumatriptan, all of which presumably act at 5-HT.sub.1D receptor subtype.
Current treatments for migraine, including sumatriptan, continue to have unwanted side effects. These include coronary vasospasm, hypertension and angina. Recent evidence suggests that sumatriptan's contraction of coronary arteries may be mediated by its stimulation of the 5-HT.sub.1B (formerly 5-HT.sub.1D.beta.) subtype of the 5-HT receptors (Kaumann, A. J. Circulation, 1994, 90:1141-1153).
Given the physiological and clinical significance of the 5-HT.sub.1D receptor, and the potential side effect liability of stimulation of its 5-HT.sub.1B receptor, it would be desirable to provide compounds that bin I with high affinity to the 5-HT.sub.1D receptor. Such compounds would be medically useful for example to treat indications such as migraine and others for which administration of a 5-HT.sub.1D ligand is indicated. Also they could be used diagnostically, for example to identify these receptors and to screen drug candidates.